The overall aim of this specialized program of translational research in acute stroke (SPOTRIAS) application is to develop new approaches to the diagnosis and treatment of acute stroke patients. The NINDS has recognized the need to develop regional interdisciplinary centers dedicated to advancing the early treatment of patients with acute stroke: they have invited applications for specialized programs in translational research in acute stroke (SPOTRIAS). The expressed intent of the SPOTRIAS program is "to support a collaboration of clinical researchers from different specialties whose collective efforts will lead to new approaches to early diagnosis and treatment of acute stroke patients". Our SPOTRIAS proposal is in direct support of this goal. The present proposal draws on several clinical and research strengths of our institution. We have built an active acute stroke team that has achieved impressive results in the rapid administration of intravenous tPA. This was accomplished through an interdisciplinary effort led by Emergency Medicine and Vascular Neurology. We serve as a major referral center for acute cerebrovascular disease and treat nearly 150 patients per year with aneurysmal subarachnoid hemorrhage. Finally, we have a large number of experienced, NIH-funded investigators dedicated to basic, translational, and clinical research in cerebrovascular disease. This multi-disciplinary group has a long-standing history of collaboration. This proposal builds on this experience and will allow us to focus attention and resources on advancing the care of patients with acute stroke. It will help to support our outreach efforts and maintain our acute stroke treatment network (Patient Access Core). It will help us train future clinician-scientists for careers in acute cerebrovascular disease (Career Development Core). It will support our efforts to maintain a repository of linked clinical information, imaging, and serum and DNA samples of stroke patients (Patient Access Core, Biospecimen Core, Data Management and Biostatistics Core, and Imaging Core). This unique dataset will be available to intramural and extramural SPOTRIAS investigators for preliminary investigation. We will investigate the effects of statins on cerebral blood flow, ischemia, and autoregulatory function in patients with aneurysmal subarachnoid hemorrhage (Project 1). We hope to expand the window and indications for iv-tPA in Project 2, a pilot study of intravenous tPA for patients with hindbrain stroke presenting with 24 hours of onset. Finally, we will evaluate a novel MR sequence for the determination of cerebral oxygenation (Project 3). This has promise as a method to reliably identify injured tissue that will progress to infarction without therapy. [unreadable]